Gene Linked to the Unrestricted Production of Immature Blood Cells in Acute Myeloid Leukemia

Overexpression of the HLX (H2.0-like homeobox) gene characterizes cancer cells in patients with acute myeloid leukemia (AML) and correlates with increased severity of the disease and shortened survival time.

Investigators at Yeshiva University (New York, NY, USA) worked with a mouse AML model as well as with cells from human AML patients to study the role of HLX in the progress of the disease.

They reported in the August 13, 2012, online edition of the journal Cancer Cell that HLX overexpression in AML mice caused blood-forming stem cells to become dysfunctional and develop into abnormal progenitors of white blood cells that continued to form replicates of themselves instead of differentiating into normal blood cells. Inhibition of HLX reduced proliferation and uncontrolled replication of leukemia cells, overcame the differentiation block, and led to prolonged survival.

Evaluation of samples from 354 human AML patients revealed that 87% of them overexpressed HLX compared to HLX expression in healthy individuals. Furthermore, it was found that among a cohort of 601 patients expressing high levels of HLX, the greater their degree of HLX expression, the worse their survival chances.

"We have discovered that a gene called HLX is expressed at abnormally high levels in leukemia stem cells in a mouse model of AML," said senior author Dr. Ulrich Steidl, assistant professor of cell biology and of medicine at Yeshiva University. "HLX is clearly a key factor in causing the over-production of white cells that occurs in AML. Our research is still in its early stages, but we are looking towards developing drugs…so we can improve treatment for AML and possibly other types of cancer."

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